Publication in EndNote Format

%0 Journal Article
%A Mario Latendresse, Jeremiah P. Malerich, Mike Travers, and Peter D. Karp
%T Accurate Atom-Mapping Computation for Biochemical Reactions
%B Journal of Chemical Information and Modeling
%I American Chemical Society
%D 2012
%K Atom Mapping, Biochemical Reactions, MetaCyc, Systems Biology
%X The complete atom mapping of a chemical reaction is a bijection of the reactant
atoms to the product atoms that specifies the terminus of each reactant atom.
Atom mapping of biochemical reactions is useful for many applications of systems
biology, in particular for metabolic engineering where synthesizing new biochemical
pathways has to take into account for the number of carbon atoms from a source
compound that are conserved in the synthesis of a target compound. Rapid, accurate
computation of the atom mapping(s) of a biochemical reaction remains elusive despite
significant work on this topic. In particular, past researchers did not validate
the accuracy of mapping algorithms. We introduce a new method for computing atom
mappings called the minimum weighted edit-distance (MWED) metric. The metric is
based on bond propensity to react and computes biochemically valid atom mappings
for a large percentage of biochemical reactions. MWED models can be formulated
efficiently as Mixed-Integer Linear Programs (MILPs). We have demonstrated this
approach on 7501 reactions of the MetaCyc database for which 87% of the models
could be solved in less than 10 s. For 2.1% of the reactions, we found multiple
optimal atom mappings. We show that the error rate is 0.9% (22 reactions) by comparing
these atom mappings to 2446 atom mappings of the manually curated Kyoto Encyclopedia
of Genes and Genomes (KEGG) RPAIR database. To our knowledge, our computational
atom-mapping approach is the most accurate and among the fastest published to
date. The atom-mapping data will be available in the MetaCyc database later in
2012; the atom-mapping software will be available within the Pathway Tools software
later in 2012.